Fluids/Electrolytes/Acid/Base

Question 1

Definition of Electrolyte

Answer 1

POS or NEG Charged molecules that give off ions when dissolved in H2O

Cation = POS
Anion = NEG

Question 2

Extracellular fluid

#3, how much contributes to TBW?
how is ECF divided?

Answer 2

1. space w/i intravascular blood vessels = 4%
2. Interstitial fluid w/i tissue = 15%
3. Transcellular = 1%
   * bile, CSF, synovial, glandular

Interstitial is 75% of ECF
Intravascular is 25% of ECF

Total = 1/3 total body water (approx 20% of bw)

Question 3

Intracellular Fluid

#3, how much contributes to TBW?

Answer 3

1. Space w/i the cells and fluid
2. Gives shape/form/functionality
3. Largest Volume of fluid in the body is INTRACELLULAR

Total = 2/3 of total body water (approx. 40% bw)

Question 4

Define:

Solutes
Ions
Electrolytes

Answer 4

1. water w/ dissolved substances w/i all body compartments
2. POS or NEG charged molecules
3. Substances given off when dissolved in water from ions → Na+/K+/Cl-/Ca++/Mg++/Phos

Question 5

Na+/K+ ATPase Pump

Answer 5

Intracellular Pump that ensures Na+ gets removed from cell and K+ stays intracellular
* majority of Na+ extracellular → 140meq/L ECF (pulls Cl- with)
* Majority of K+ intracellular (140meq/L ICF)

Ex: Beta Blockers → propanolol blocks Na+/K+ ATP pump

Question 6

Intracellular Cation and Anions

Answer 6

Cations = K+ Mg++
Anions = Phos (needed for ATP and to bind to glucose)
* Blood proteins (mainly NEG charged)

Question 7

Extracellular Cations and Anions

Answer 7

Cations = Ca++, Na+ (Na+/K+ pump)
Anions = Cl- → net from Na+/K+ pump
* HCO3- →ECF reserves are alkaline to buffer acids inside the cell
* Cl- → follows Na+

Question 8

Anion Gap

Answer 8

Difference between measured Cations and anions in the blood
–numerous unmeasured anions = ↑
anion gap to maintain zero net electric plasma charge (Cations and Anions must always equal)

Normal K9= 10-24 mmol/L Fel= 13-27 mmol/L

Question 9

7

Examples of unmeasured Anions

Answer 9

Lactate
Ketones
Ethylene glycol
Uremia
Aspirins
Alcohols
cyanide

Question 10

OsmolARITY

Answer 10

concentration of a solution expressed as mOsm/L

LAR=LITER

Question 11

OsmolALITY

Answer 11

concentration of a solution expressed as mOsm/kg

Normal = K9 = 290-310 mOsm/kg Fel= 290-330 mOsm/kg

Question 12

Tonicity

3 types

Answer 12

Ability of extracellular solutions to move water in or out of cell via osmosis
Isotonic = do not cause changes in h20 movement across cell membrane
Hypotonic = tonicity LESS than plasma causes H2O to move INTO cells
Hypertonic = tonicity HIGHER than plasma, causes fluid to move OUT of cells into fluid

“effective osmolality”

Question 13

Osmotic Pressure

Definition
Effects of HyperNa+ and HypONa+ on water

Answer 13

Pressure needed applied to H20 to prevent osmosis (movement of water)

HyperNa+ → cells volume loss due to osmotic gradient pushing water into hyperosmolar extracellular space
HypoNa+ → cells SWELL as H2O gets pushed into cells

Ex: Na+ and Glucose

WATER FOLLOWS Na+

Question 14

Ca++ ATP pump

What is it exchanged for?
Which system utilizes this?

Answer 14

Ca++ moves outside cell when Na+ shifts intracellularly
“couter-transport”
– enters the plasma by absorption from the gastrointestinal tract regulated by vitamin D and by resorption from the bones.
– leaves the plasma by secretion into GIT, urinary excretion, and deposition into bones
–important for muscle activity/contrations
–nerve impulse transmissions
–blood clotting

Ex: Digoxin → inhibits Na+/K+ ATP exchange, Na+ stays in ECS → Ca++ stays ICS for contractility improvement

Question 15

H+ ATPase pump

Answer 15

– H+-K+-ATPases are ion pumps that use the energy of ATP hydrolysis to transport protons (H+) in exchange for (K+).
– Dumps acid ASAP in metabolic acidosis

Proximal Convuluted tubule in Kidney

HCO3 is later reabsorbed as buffer

Question 16

Free water deficit definition

Answer 16

–determines the volume (L) of water required to correct dehydration or, to reach the desired level of sodium in the blood serum
Does Not Follow Lytes
H2O w/o solutes
–Kidney depends on Free H2O to concentrate/dilute urine influenced by ADH
–Deficits occur w/ solute-free water loss from body

2nd to CKD/D+/V+/Panc/Peritonitist/FBO/DI/Adipsia/Lack of water access

Question 17

Law of Electroneutrality

Answer 17

any single ionic solution, sum of negative charges attracts an equal sum of positive chargers concentration of cations = concentration of anions

Question 18

Na+ review

Normal vs Disturbances

Answer 18

Normal actions: TBW inverse relation with Na+
–fluid regulation
osmosis → H2O FOLLOWS Na+
Distrubances: cells shrink or swells w/i brain → mental abnormalities
–free water deficit
–toxicity (play dough)
–sz/ataxia/behavioral changes/lethargy

Main Na+ ECF cation

Question 19

K+ Review

Normal vs Disturbances

Answer 19

Normal actions: resting membrane potential → needed for action potential and repolarization of myocaridal cells
–absorbed in SI/excreted by kidneys and colon
Disturbances: membrane potential problems → arrhythmias
–affected by acid-base disturbances → low pH = high K+; high pH = low K+
–affected by lack of insulin
–Reperfusion syndrome → increase in insulin stimulates intracellular uptake of K+/phos-
–bradycardia/tall T-waves/ Small P-waves

Intracellular cation (99%)

Question 20

Ca++ Review

Normal vs Disturbances

where is it stored?
What regulates it?

Answer 20

Normal actions: stored in bones; absorbed thru diet

– HypOCa++ = ↑ permeability to Na+ → action potential = ↑↑ excitability
– HypERCa++= ↓ permeability to Na+ = ↓ action potential = ↓↓ excitability
–PTH controls ECF Ca++ (and Phos) Calicitonin via C-cells

Question 21

Mg++ Review

Normal vs Disturbances

where is it stored/absorded?
what transports is it apart of?

Answer 21

Normal actions: stored in bones/absorbed in SI
–affects active transport or Na+/K+ ATP pump
–blocks Ca++ channels intracellularly
Disturbances: Nerve/muscle problems → twitching/ faciculations
–arrhythmias
–associated with other lyte derangements → refractory hyPOCa++/hyPO K+ (active transport)

Question 22

Cl- Review

Normal vs Disturbances

Where is it absorbed? What is it reguated by?

Answer 22

Normal actions: Needed for acid/base balance
–absorbed from diet
–regulated by kidney
Disturbances: associated with body water disturbances
–will cause opposite changes to HCO3 → hyPO will raise, hyPER will lower
– ↓ with GI losses

Major Extracellular Anion

Question 23

Phos Review

Normal vs Disturbances

What is responsible for regulating it?

Answer 23

Normal actions: absorbed/excreted along with Ca++
–Mineral for bone strength
–ATP phos bond carries energy for ALL CELL functions
–buffers bone/serum/urine
Disturbances: ↑ PTH = ↑ Ca++ = ↑ Phos excreted = hyPOphos
– ↓ GFR = ↓ Phos excreted =hypERphos
–Insulin causes Phos to shift intracellularly
–Refeeding syndrome

Major intracellular Anion

Question 24

5

ECF Osmoles

Answer 24

Na+
Glucose
Urea
K+
Cl-

Question 25

Effective vs Ineffective osmoles

Examples of each
How do they affect water movement?

Answer 25

Effective: Do not freely cross cell membrane → Na+/Glu/K+
* Na+/K+ pump is what moves molecules across membrane
Ineffective: Freely crosses cell membrane → Urea (cannot create osmotic gradient)

Retention incites H2O to cross membrane toward side w/ higher concentration of effective osmoles

Question 26

Na+/Glu Co-Transporter

Answer 26

responsible for maximizing the absorption of glucose from the intestinal tract and the recovery of glucose from the proximal tubule of the kidney following glomerular filtration

Facillitated diffusion *Glu follows Na+

Question 27

Na+/H+ Exchange

Answer 27

–Na+ is exchanged for H+ (Na+ IN H+ OUT) → PCT
–Utilized during metabolic acidosis

PCT → CO2 + H2O = H2CO3 (carbonic acid) → HCO3 + H+ (bicarb get reabsorbed in peritubule capillary and H+ gets excreted in distal convuluted tubule

Question 28

Obligated Water

Example, what is responsible for reabsorption?

Answer 28

Obligated to follow Electrolytes
–H2O obligated to follow Na+
– Aldosterone responsible for reabsorbing obligated water

Question 29

HCO3/Cl- Transporter

Answer 29

–HCO3 is exchanged for Cl-

Question 30

Na+ Regulators
Absorption
Excretion

Answer 30

–Thirst/AldosteroneADH main regulators
–absorbed in PCT/ALOH via carrier protein
–cotransport of Glu/AA
–exchanged for H+/ammonium/K+ when reabsorbed

Question 31

K+ Regulators
Absorption
Excretion

Answer 31

–Reabsorped in PCT/ALOH/DCT

Question 32

H+
Absorption
Excretion

Answer 32

–PCT H+ is sent out in exchanged for Na+
–DCT H+ →Alpha intercalated cells use ATP to pump H+ into urine
–Ammonium combines with H+ in DCT to become a weak acid (keep urine pH from dropping too low)

Question 33

Renal buffer system

Answer 33

homeostatic mechanism that uses the kidneys to help maintain the acid-base balance by excreting either an acidic or alkaline urine in response to changes in the hydrogen ion concentration of body fluids. Renal buffering involves a complex series of reactions within kidney tubules.

Question 34

Osmolar Gap

Answer 34

Measure - Calculated
–does not exist just missing pieces of the equation!

If difference > 10 there is a problem

Question 35

Osmosis

Answer 35

movement of water from a high concentration to a low concentration
–membrane permeable to WATER not the SOLUTES

Na+ is KING of osmosis

Question 36

Interstital Fluid

Answer 36

formed by filtration of fluid out of microvessels and removed via the lymphatic system or transudation across the serosal surface of the organ

Question 37

Interstitial fluid pressure

what does it mediate?
what does it inhibit?
what is it dependent on?

Answer 37

– responsible for mediating the balance between microvascular filtration and the two interstitial outflows
– ↑= inhibits filtration and promotes lymph flow and serosal transudation
– interstitial fluid volume dependent on pressure and its relationship with the current volume

Question 38

Microvascular filtration

What is it comprised of? what directly effects it?

Answer 38

– Endothelial glycocalyx is primarily the barrier to microvascular filtration
– COP of fluid on the interstitial side of the glycocalyx and w/i endothelial clefts has more direct effect on filtration than that of bulk interstitial fluid

Question 39

What is the glycocalyx comprised of?

Answer 39

glycoproteins, proteoglycans, and glycosaminoglycans that form a layer attached to the luminal surface of vascular endothelial cells

Question 40

Starling-Landis equation

Answer 40

– direction of microvascular filtration depends on the sum of the hydrostatic and colloid osmotic pressure gradients
– magnitude of filtration is the product of the
hydraulic conductivity,
surface area, and net pressure gradient.

Question 41

COP of plasma

Answer 41

– consequence of the concentration of proteins, particularly albumin, as well as the redistribution of permeable ions induced by the presence of charges on those proteins

Question 42

Lymphatic drainage

Where does this start and end? Where is this utilized?

Answer 42

Removes interstitial fluid and returns it to the venous blood
– begins with terminal lymphatic vessels w/i interstitial space → larger vessels through lymph nodes, → terminates in the venous system
–Pleural fluid and peritoneal fluid removed by lymphatic drainage to return to venous circulation

Question 43

What factors regulate Lymph flow?

#7

Answer 43

modified by numerous vasoactive mediators:
prostaglandins
thromboxane
nitric oxide
epinephrine
acetylcholine
substance P - neurotransmitter and a neuromodulator
bradykinin - peptide that promotes inflammation

Question 44

What do lymphatic vessels respond to?

Answer 44

– increased outflow pressure by increasing pumping activity via increases in the strength and frequency of contractions.

Question 45

Serosal transudation

Answer 45

Edema-induced increases in interstitial hydrostatic pressure will increase the rate of transudation and may result in effusion within the surrounding cavity of suspended organs

Question 46

Antiedema mechanisms

#4

Answer 46

intrinsic interdependent mechanisms include:
(1) increased interstitial hydrostatic pressure
(2) increased lymph flow
(3) decreased interstitial colloid osmotic pressure
(4) increased trans-serosal flow in organs within potential spaces

they incur little energy cost and are effective because they respond rapidly to edema formation

Question 47

Mechanisms of edema formation

x5

Answer 47

1. Venous hypertension → Increased microvascular pressure and filtration
2. Hypoproteinemia → Decreased plasma colloid osmotic pressure, increased filtration
3. Increased microvascular permeability → Increased filtration
4. Impaired lymph flow →Vessel obstruction or damage
5. Increased negativity of interstitial fluid pressure → Shift in interstitial pressure–volume relationship, decreased interstitial pressure

Question 48

Regulation of plasma osmolality

What mechanisms regulate plasma osmolality?

Answer 48

Hypothalamic osmoreceptors sense changes in plasma osmolality, and changes of only 2–3 mOsm/L induce compensatory mechanisms to return the plasma osmolality to its hypothalamic setpoint
– two major physiologic mechanisms for controlling plasma osmolality are the antidiuretic hormone (ADH) system and thirst

Question 49

ADH

Definition, where does it come from?
What is it stimulated by?

Answer 49

ADH is a small peptide secreted by the posterior pituitary gland
Stimulated by:
– elevated plasma osmolality
– decreased effective circulating volume.

Question 50

Osmoreceptors

How to do they stimulate ADH release?

Answer 50

Specialized group of cells in the hypothalamus
– with ↑ plasma osmolality = cell shrinkage → send impulses via neural afferents to the posterior pituitary → stimulate ADH release

Question 51

How is ADH stimulated by low circulating volume?

How does it fix it?

Answer 51

When effective circulating volume is low, baroreceptor cells in the aortic arch and carotid bodies send neural impulses to the pituitary gland that stimulate ADH release
– H2o crosses into the hyperosmolar renal medullary interstitium and into the vasa recta along its osmotic gradient; the H2o is then returned to the general circulation

Question 52

Aquaporin channels

Answer 52

Aquaporins are channels that allow water to move from the tubular lumen into the renal tubular cell

Question 53

ADH effect on Aquaporin channels

What receptor does it activate?

Answer 53

When ADH activates the V2 receptor on the renal collecting tubular cell, aquaporin-2 molecules insert into the cell’s luminal membrane

Question 54

Lack of ADH in Renal tubular collecting ducts =

Answer 54

become impermeable to water

Question 55

Hyperosmolality effect on Thirst

Answer 55

Stimulate thirst
– The mechanisms by which hyperosmolality and hypovolemia stimulate thirst are similar to those that stimulate ADH release

Question 56

Role of RAAS and ADH for effective circulation volume regulation

Answer 56

RAAS = monitors and fine-tunes effective circulating volume
ADH system maintains normal plasma osmolality

Question 57

Which is more important effective Circulating volume or plasma osmolality?

Answer 57

maintenance of effective circulating volume is prioritized over maintenance of normal plasma osmolality, so in patients with poor effective circulating volume, thirst and ADH release increase irrespective of plasma osmolality

Question 58

How does an increase in water intake affect Na+?

Answer 58

increased water intake (from drinking) and water retention (from ADH action at the level of the kidney) decrease plasma [Na+] and can lead to hyponatremia (and thus hypoosmolality) in patients with poor effective circulating volume

Ex: Chronic heart failure patient with hyponatremia

Question 59

Total body sodium content versus plasma sodium concentration

Answer 59

Plasma Na+ concentration independent from TB Na+ content
TB Na+ content = total # of sodium molecules in the body, regardless of the ratio of sodium molecules to water molecules.

Question 60

How is Hydration status determined?

Answer 60

Na+ content determines the hydration status of the animal
– dehydrated, euhydrated, overhydrated

Question 61

Overhydration

Answer 61

– increased total body sodium
– increased quantity of fluid is maintained within the interstitial space and the animal appears overhydrated, regardless of the [Na+].

Question 62

Dehydration

Answer 62

– decreased total body sodium content
–decreased quantity of fluid is maintained within the interstitial space and the animal appears dehydrated, regardless of the [Na+].
– hypovolemia occurs because fluid moves from IVS into the interstitial space
– as a result of decreased interstitial hydrostatic pressure = fluid deficit in the intravascular space

Question 63

Cause for hyperNa+ :
Water deficit – excessive water loss

#5

Answer 63

1. Renal water loss
2. Osmotic diuresis due to glucosuria or mannitol causes an electrolyte-free water loss = hyperNa+ in sick animals with no water access
3. Diabetes insipidus (DI), a syndrome of inadequate release of or response to ADH
4. GI losses
5. Cathartic-containing Activate charcoal administration = pulls lyte-free H2O from ECS to GIT

Question 64

Diabetes insipidus

Answer 64

DI pts depend on oral water intake to maintain normal plasma [Na+] because they cannot adequately reabsorb free water in the renal collecting duct
– become severely hypernatremic when they do not drink and hold down water

Question 65

Cause for hyperNa+ :
Water deficit – inadequate water intake

#2

Answer 65

1. hypernatremic if denied access to water for extended periods
2. syndrome of hypodipsic hypernatremia has been reported in Miniature Schnauzers → due to impaired osmoreceptor or thirst center function.

Question 66

Cause for hyperNa+ :
Increased sodium intake or retention

#4

Answer 66

Severe hypernatremia introduction of large quantities of sodium
1. hypertonic fluid administration (hypertonic saline, sodium bicarbonate)
2. sodium phosphate enemas
3. ingestion of seawater, beef jerky, or salt-flour dough mixtures.
4. Hyperaldosteronism can also cause hypernatremia due to excessive renal sodium retention

Question 67

Clinical signs of hypernatremia

Answer 67

severe (usually >170 mEq/L) or occurs rapidly, – – Neurons intolerant of the cell volume change – CNS signs such as obtundation, head pressing, seizures, coma, and death are the signs most commonly associated with clinical hypernatremia.

Slow hyperNa+ typically asymptomatic

Question 68

Physiologic adaptation to hypernatremia

Answer 68

cells w/ Na+/K+-ATPase pumps lose volume (shrink) from hyperNa+ → water moves freely through the water-permeable cell membrane while these plentiful electrolytes do not
–causes free water to move out of the relatively hypOosmolar ICS into hyperosmolar ECS = decreased cell volume.
– brain has adaptive ways to protect against neuronal water loss

Question 69

Cerebral protective mechanisms from HyperNa+

Answer 69

– neuronal water is lost to the hyperNa+ circulation, ↓ interstitial hydrostatic pressure draws fluid from CSF into the brain interstitium
– As plasma osmolality rises, Na+ and Cl- move rapidly from CSF into cerebral tissue → helps minimize brain volume loss by ↑ neuronal osmolality = drawing water back into the cells
– w/i 24hr, neurons begin to accumulate organic solutes to ↑ intracellular osmolality and help shift lost water back into the cell

Question 70

Organic solutes/Idiogenic osmoles aka osmolytes

Answer 70

molecules such as inositol and glutamate
– Generation and retention of these idiogenic osmoles begin within a few hours of neuron volume loss, though full compensation may take as long as 2–7 days

Question 71

Normovolemia and HyperNa+

Answer 71

Hypernatremia should be treated even w/ no CS
– minor changes in [Na+] have been associated with poor outcome in people
– Patients with hyperNa+ have a water deficit = water should be replaced using fluid with a lower effective osmolality than the patient’s.
– [Na+] can be decreased by 0.5–1 mEq/L/hr in most situations of chronic or subacute hypernatremia without complication

Question 72

Water supplementation

IV vs orally

Answer 72

Water may be supplemented intravenously (as 5% dextrose in water) or orally on an hourly schedule in animals that are alert, willing to drink, and not vomiting.

Free water deficit calculation

Question 73

When clinical signs of hypernatremia are present

Answer 73

water replacement must be more rapid
Recent recommendation in people is to drop [Na+] in such cases by 2 mEq/L/hr until the [Na+] is high-normal

Question 74

Treatment of acute sodium intoxication

Answer 74

– some authors recommend rapid infusion of 5% dextrose in water paired with hemodialysis to restore normal [Na+] as calculated using the water deficit equation
– When hemodialysis is not possible, aggressive water replacement over ≤12 hours seems reasonable

Question 75

Free water replacement with Cardiac or Kidney Dz

Answer 75

relatively safe, even in animals with cardiac or kidney disease, because the two-thirds of the infused volume that enters the cells cannot cause “fluid overload” or edema

Question 76

Hyponatremia

#4

Answer 76

CS 2nd, uncommon in critically ill dogs and cats because signs are not usually seen unless [Na+] is very low, usually <120 mEq/L
– Causes:
1. Decreased effective circulating volume
2. Hypoadrenocorticism
3. Renal tubular dysfunction: Diuretics, kidney failure
4. Syndrome of inappropriate antidiuretic hormone secretion

Question 77

Causes of HypoNa+:
Decreased effective circulating volume

Answer 77

– leads to ADH release and water intake in defense of intravascular volume = decreases [Na+].
– CHF, Body cavity effusions, Edematous states → RAAS activation with increase water retention
– GI or Urinary Loss → compensatory drinking and retention

Question 78

Causes of HypoNa+:
Hypoadrenocorticism

Answer 78

– leads to hypoNa+ via decreased sodium retention (caused by hypoaldosteronism) combined with increased water drinking and retention in defense of inadequate circulating volume
– low circulating cortisol concentration leads to increased ADH release and resultant water retention regardless of intravascular volume status
– Animals w/ atypical hypoadrenocorticism, whose aldosterone production and release are normal, may also develop hyponatremia.

Question 79

Causes of HypoNa+:
Renal tubular dysfunction: Diuretics, kidney failure

Answer 79

Loop or thiazide diuretic use causes hyponatremia by induction of hypovolemia, hypokalemia causing Na+ ions to shift INTO cells in exchange for K+ ions, and the inability to create dilute urine
– Kidney failure can cause hyponatremia by similar mechanisms.

Question 80

Causes of HypoNa+:
Syndrome of inappropriate antidiuretic hormone (ADH) secretion

Answer 80

Syndrome of inappropriate ADH secretion causes hyponatremia through water retention in response to improperly high circulating concentrations of ADH

Question 81

Clinical signs of hyponatremia

Answer 81

cells w/ Na+/K+-ATPase pumps swell from hyponatremia b/c water moves into the relatively hyperosmolar cell from the hypoosmolar ECS
– CNS signs consistent with cerebral edema, such as obtundation, head pressing, seizures, coma, and ultimately death from brain herniation.

Question 82

Physiologic adaptation to hyponatremia

Answer 82

Interstitial and intracellular CNS edema increases intracranial tissue hydrostatic pressure
– pressure enhances fluid movement out of neurons and into the CSF, which flows out of the cranium, through the subarachnoid space and central canal of the spinal cord, and back into venous circulation
– Swollen neurons also expel solutes such as Na+/K+ and organic osmolytes to decrease intracellular osmolality and encourage water loss to the ECF, returning cell volume toward normal.

Question 83

osmotic demyelination syndrome (ODS), or myelinolysis

Answer 83

Complications of HypoNa+ treatment
– ODS is the result of neuronal shrinking away from the myelin sheath as water moves out of the neuron during correction of hyponatremia.
– myelinolysis commonly seen in thalamus
– CS usually manifest days after intervention, so the clinician cannot assume that a rapid change in plasma [Na+] has been well tolerated simply because no CNS signs are present during initial treatment.

limb paresis, dysphagia, ataxia, and disorientation

Question 84

Rapid correction of HypONa+ can lead to:

Answer 84

Overzealous correction of severe hyponatremia has led to paresis, ataxia, dysphagia, obtundation, and other neurologic signs in dogs

Question 85

Treating asymptomatic hyponatremia

Answer 85

– hyponatremia caused by decreased effective circulating volume usually evolves over time
– Hyponatremia due to poor effective circulating volume usually self-corrects with improvement in perfusion, as ADH secretion drops and water is eliminated by the kidney
– Asymptomatic patients that are edematous may be treated with water restriction alone, and those that are asymptomatic and normally hydrated or dehydrated may be treated with administration of fluids with a sodium concentration that exceeds the patient’s [Na+].

Question 86

Correction rate for hypoNa+

Answer 86

chronic or the evolutionary timeline is unknown, the goal is to raise patient [Na+] by no more than 10 mEq/L during the first 24 hours and by no more than 8 mEq/L during each following 24-hour period, not to exceed the low end of the reference interval some authors recommend an increase of no more than 8 mEq/L over any 24-hour period, particularly if risk for ODS is high due to severity or chronicity of the hyponatremia.

Question 87

Effect of HypoK+ supplementation with HypoNa+

Answer 87

when correcting hyponatremia in animals being treated for concurrent hypokalemia → potassium supplementation will speed the correction of hyponatremia.

Question 88

Cerebral Edema from severe acute HypoNa+

Answer 88

rapid water influx into neurons may exceed these cells’ ability to expel solute and water quickly enough
– Cerebral edema is treated with 7.0%–7.5% sodium chloride (hypertonic saline) at 3 to 5 ml/kg over 20 minutes.

Question 89

Pseudohyponatremia

Answer 89

hyponatremia in a patient with normal or elevated plasma osmolality
– most common cause in dogs and cats is hyperglycemia
– when hyperglycemia is present, the excess glucose molecules cause an increase in ECF water, diluting sodium to a lower concentration.
– other common cause is mannitol infusion with retention (rather than renal excretion) of mannitol molecules

Question 90

Hyperglycemia relationship to Sodium level

Answer 90

For each 100 mg/dl increase in blood glucose, [Na+] drops by approximately 1.6–2.4 mEq/L.

Question 91

% of K+ located intracellular

Answer 91

99%

Question 92

Where do majority of intracellular K+ reside?

Answer 92

Skeletal muscle cells

Question 93

Average potassium concentration

Answer 93

K+ concentration in intracellular space of dogs and cats is 140 mEq/L
– plasma space averages 4 mEq/L.
– Serum potassium levels therefore do not reflect whole body content or tissue concentrations.

Question 94

Body’s potassium regulation

#5

Answer 94

pH regulation
changes in osmolality
insulin
catecholamines
aldosterone

Question 95

Solvent drag

Answer 95

Hyperosmolality causes the translocation of water from the cellular space, which drags cellular potassium into the extracellular fluid space

Question 96

Hormone effects on K+

x3

Answer 96

Insulin, catecholamines, and aldosterone transfer potassium from the extracellular space to the intracellular space.

Question 97

Aldosterone effect on K+

Answer 97

Any increase in extracellular fluid potassium concentration triggers aldosterone release, which acts at the** distal renal tubules to increase Na-K-ATPase activity**
– promotes the transluminal transfer of potassium ions through the collecting duct principal cells into the renal tubular lumen, thus allowing for potassium excretion and sodium reabsorption.

Question 98

Kaliuretic feedforward control

Where are the sensors? What effects does it cause?

Answer 98

responds to signals in the external environment and involves sensors in the stomach and the hepatic portal regions
– sensors detect local changes in potassium concentrations resulting from potassium ingestion and signal the kidney to alter potassium excretion to restore potassium balance
– done without the influence of aldosterone.

Question 99

Hypokalemia: causes

Answer 99

(1) disorders of internal balance
Metabolic alkalosis
Insulin administration
Increased levels of catecholamines
β-Adrenergic agonist therapy or intoxication
Refeeding syndrome
(2) disorders of external balance
Renal potassium wasting
Prolonged inadequate intake
Diuretic drugs
Osmotic or postobstructive diuresis
Chronic liver disease
Inadequate parenteral fluid supplementation
Aldosterone-secreting tumor or any cause of hyperaldosteronism
Prolonged vomiting associated with pyloric outflow obstruction
Diabetic ketoacidosis
Renal tubular acidosis
Severe diarrhea
Ingestion of barium-containing party sparklers glucocorticoid drugs
Glucocorticoid drug administration

Question 100

Neuromuscular effects of HypoK+

Answer 100

K+ necessary for maintenance of normal resting membrane potential
– neuromuscular abnormality induced by hypokalemia in dogs and cats is skeletal muscle weakness from hyperpolarized (less excitable) myocyte plasma membranes that may progress to hypopolarized membranes.
– ventroflexion or head neck, stiff gait, plantagrade stance

Question 101

HypoK+ effect on myocardial cells

Answer 101

high intracellular/extracellular potassium concentration ratio induces a state of electrical hyperpolarization leading to prolongation of the action potential
– predisposes patient to atrial and ventricular tachyarrhythmias, atrioventricular dissociation, and ventricular fibrillation

Question 102

HypOK+ EKG findings

Answer 102

Canine ECG abnormalities include depression of the ST segment and prolongation of the QT interval
– Increased P wave amplitude, prolongation of the PR interval, and widening of the QRS complex may also occur
– predisposes to digitalis-induced cardiac arrhythmias
– causes the myocardium to become refractory to the effects of class I antiarrhythmic agents (i.e., lidocaine, quinidine, and procainamide).

Question 103

Causes of Hyperkalemia: Increased intake or supplementation

#10

Answer 103

1. Intravenous potassium-containing fluids
2. Expired RBC transfusion
3. Drugs (potassium penicillin G, KCl, KPhos)
4. Translocation from ICF to ECF
5. Mineral acidosis (respiratory acidosis, NH4Cl, HCl, uremia)
6. Insulin deficiency
7. Acute tumor lysis syndrome
8. Extremity reperfusion following therapy for thromboembolism
9. Drugs (nonspecific β-blockers, cardiac glycosides)
10. Cardiopulmonary arrest

Question 104

Causes of Hyperkalemia: Decreased urinary excretion

#12

Answer 104

1. Anuric or oliguric renal injury
2. Urethral obstruction, bilateral ureteral obstruction
3. Uroabdomen
4. Hypoadrenocorticism
5. Gastrointestinal disease (trichuriasis, salmonellosis, perforated duodenum)
6. Chylothorax or pleural or peritoneal effusions
7. Drugs (ACE inhibitors, angiotensin receptor blockers, heparin, cyclosporine and tacrolimus, non-steroidal anti- inflammatory drugs, trimethoprim)
8. Pseudohyperkalemia
9. Thrombocytosis or leukocytosis (>1,000,000 platelets or >100,000 leukocytes)
10. Akita dog and other dogs of Japanese origin (secondary to in-vitro hemolysis)
11. Idiopathic
12. General anesthesia in healthy dogs (most notably Greyhounds)

Question 105

HyperK+ with Mineral Acidosis

Answer 105

-respiratory acidosis, uremia or pharmacologic induction by ammonium chloride, hydrogen chloride, or calcium chloride infusions
– causing potassium to move out of the intracellular space in exchange for hydrogen ions.

Question 106

HyperK+ with Diabetes

#3

Answer 106

• insulin deficiency that results in a decreased cellular uptake of potassium
• hyperosmolality that potentiates potassium translocation with water due to “solute drag” effect
• decreased potassium excretion related to renal dysfunction (comorbidities, a prerenal component, or an acute kidney injury relative to hypovolemia/perfusion).

Question 107

EKG changes with HyperK+

#6

Answer 107

1. peaked, narrow T waves
2. prolonged QRS complex and interval
3. depressed ST segment
4. depressed P wave
5. atrial standstill
6. ventricular flutter/fibrillation

Question 108

HyperK+ from Renal Dz

what is it dependent on? where does this take place in the kidney?

Answer 108

– distal tubule is dependent on both adequate glomerular filtration rate and urine flow to excrete potassium
– severe reduction in both of these determinants with acute kidney injury significantly impairs the ability of the distal tubule to excrete sufficient potassium

Question 109

HyperK+ from hypoadrenocorticism

Answer 109

In the absence of aldosterone, the resulting natriuresis causes a reduced effective circulating volume, which further impairs distal tubule potassium excretion.

Question 110

Pseudohyperkalemia

Answer 110

Potassium can be released from increased numbers of circulating blood cells, especially platelets and leukocytes, causing an artifactual increase in potassium
– Akitas/japanese dogs

Question 111

Consequences of HyperK+

#3

how does it affect cardiac myocytes?

Answer 111

causes changes in cardiac myocyte excitation and conduction
– the concentration gradient across the cardiac cell membranes is reduced, leading to a less negative resting membrane potential = makes cardiac cell membranes more excitable.
– inactivates some of the Na+/K+ channels during the resting phase, making these cells slower to reach threshold potential
– Acidemia results in extracellular shift in potassium as well as decreasing the β-adrenergic receptors in cardiac tissues.

Question 112

HyperK+ treatment: Ca++ Gluconate

Answer 112

– antagonize cardiotoxic effects of hyperK+
– Increases threshold voltage but will not lower serum potassium

Question 113

HyperK+ treatment: HCO3-

Answer 113

Causes metabolic alkalosis allowing for potassium to move intracellularly, paradoxical CNS acidosis with rapid administration

Question 114

HyperK+ treatment: 50% Dextrose

Answer 114

Allows for translocation of potassium into the intracellular space in the presence of endogenous insulin

Question 115

HyperK+ treatment: Terbutaline

Answer 115

Stimulates Na+/K+-ATPase to cause translocation of potassium into the cell

Question 116

Calcium homeostasis

Answer 116

necessary for muscle contraction, neuromuscular function, and skeletal bone support

Question 117

Three forms of circulating calcium exist in serum and plasma:

Answer 117

1. ionized (free),
2. protein bound
3. complexed (calcium bound to phosphate, bicarbonate, lactate, citrate, oxalate)
   Total calcium measures all 3

Question 118

Ionized Ca++

Answer 118

biologically active form in the body and is considered the most important indicator of functional calcium levels

Question 119

Calcium regulation

where does it occur? what organs are involved?

Answer 119

complex process involving primarily parathyroid hormone (PTH), vitamin D metabolites, and calcitonin
– most of their effects seen on the intestine, kidney, and bone

Question 120

primarily parathyroid hormone (PTH)

what inhibits/stimulates it?

what is it secreted by?

Answer 120

synthesized and secreted by the chief cells of the parathyroid gland in response to hypocalcemia
–normally inhibited by increased serum ionized calcium levels, as well as by increased concentrations of circulating calcitriol

Question 121

How does PTH increase Ca++ levels?

#3

Answer 121

through increased tubular reabsorption of calcium
increased osteoclastic bone resorption increased production of calcitriol that then increases intestinal absorption of calcium

Question 122

Vitamin D and its metabolites

Answer 122

– Cats and Dogs depend on Vit D in their diet
– cannot photosynthesize Vit D efficiently from their skin (like humans)
– After ingestion and uptake, vitamin D (cholecalciferol) is first hydroxylated in the liver and then it is further hydroxylated to calcitriol by the proximal tubular cells of the kidney
– final hydroxylation by the 1α-hydroxylase enzyme system to form active calcitriol

Question 123

Calcitriol Synthesis

What effects its levels?
where does it act primarily?

Answer 123

• Decreased levels of phosphorus, calcitriol, and calcium promote calcitriol synthesis
• Increased levels of these substances all cause a decrease in calcitriol synthesis.
• calcitriol primarily acts on the intestine, bone, kidney, and parathyroid gland

Question 124

Calcitriol MOA in instestine

Answer 124

In the intestine, calcitriol enhances the absorption of calcium and phosphate at the level of the enterocyte

Question 125

Calcitriol MOA in bones

Answer 125

– promotes bone formation and mineralization by regulation of proteins produced by osteoblasts
– also necessary for normal bone resorption because of its effect on osteoclast differentiation

Question 126

Calcitriol effects on Kidneys

Answer 126

calcitriol acts to inhibit the 1α-hydroxylase enzyme system, as well as promote calcium and phosphorus reabsorption from the glomerular filtrate

Question 127

Calcitriol effects on parathyroid

Answer 127

calcitriol acts genomically to inhibit the synthesis of PTH

Question 128

HARDIONS G

Hypercalcium differentials

Answer 128

Hyperparathyroidism
Addison’s disease
Renal failure
Vitamin D toxicosis e.g. from rodenticides, house plants or psoriasis creams
Idiopathic (this is mainly a feline condition)
Osteolytic e.g. osteomyelitis
Neoplasia e.g. lymphoma, anal sac adenocarcinoma
Spurious i.e. rule out lab error before starting investigation
Granulomatous disease

diagnosis of hypercalcemia is confirmed with an ionized calcium measurement generally greater than 6 mg/dl or 1.5 mmol/L in the dog or greater than 5.7 mg/dl or 1.4 mmol/L in the cat.

Question 129

CS of HyperCa++

Answer 129

– polyuria and polydipsia (uncommon in cats), anorexia, constipation, lethargy, and weakness – Severely affected animals may display ataxia, obtundation, listlessness, muscle twitching, seizures, or coma
– EKG abnormalities

Question 130

EKG abnormalities with HyperCa++

Answer 130

Bradycardia may be detected on physical examination
– prolonged PR interval, widened QRS complex, shortened QT interval, shortened or absent ST segment, and a widened T wave.

Question 131

neoplasia-associated hypercalcemia

Answer 131

specifically lymphoma, the most common cause in dogs

Question 132

Type of Rat poison causing HyperCa++

Answer 132

Rat bait containing cholecalciferol

Question 133

HyperCa++ Crisis

Answer 133

Question 134

HyperCa++ Treatment

Answer 134

Definitive treatment for hypercalcemia involves removing the underlying cause
– Acute therapy often involves the use of one or more of the following: intravenous fluids, diuretics (furosemide), glucocorticoids, and calcitonin

Question 135

therapeutic fluid of choice for HyperCa++

Answer 135

0.9% sodium chloride
– additional sodium ions provide competition for renal tubular calcium reabsorption, resulting in enhanced calciuria
– In addition, 0.9% sodium chloride is calcium-free, unlike other isotonic crystalloids

Question 136

How does HyperCa++ cause hypertension?

Answer 136

hypercalcemia can contribute to the development of hypertension secondary to vasoconstriction

Question 137

Furosemide’s affect on Ca++

Answer 137

enhances urinary calcium loss
– calciuresis

Question 138

Glucocorticoid affects on Ca++

#3

Answer 138

can cause a reduction in serum calcium concentration
– reduced bone resorption
– decreased intestinal calcium absorption
– increased renal calcium excretion

Question 139

Calcitonin effects for HyperCa++ tx

Answer 139

Calcitonin acts to decrease serum calcium concentrations mostly by reducing the activity and formation of osteoclasts

Question 140

HCO3- effects for HperCa++ tx

Answer 140

decreases the ionized and total calcium

Question 141

Bisphosphonates for HyperCa++ tx

Answer 141

decrease osteoclastic activity, thus decreasing bone resorption
– not considered drugs of choice for acute or crisis therapy
– can cause esophageal irritation and have been reported to cause abdominal discomfort, nausea, and vomiting in humans
– Bone toxicity from long-term treatment with bisphosphonates has been reported

Pamidronate, zoledronate

Question 142

Hypocalcemia

x3 causes

Answer 142

Decreased total serum calcium is particularly common in those with low circulating albumin status
– common for cats with pancreatitis to have ionized hypocalcemia
– Eclampsia in dogs

Question 143

Clinical Signs Associated with Hypocalcemia

List as many you can think of

Answer 143

1. Muscle tremors or fasciculations
2. Facial rubbing
3. Muscle cramping
4. Stiff gait
5. Behavioral change
6. Restlessness or excitation
7. Aggression
8. Hypersensitivity to stimuli
9. Disorientation
10. seizures
11. Panting
12. Pyrexia
13. Lethargy
14. Anorexia
15. Prolapse of third eyelid (cats)
16. Posterior lenticular cataracts
17. Tachycardia or ECG alterations (i.e., prolonged QT interval)
    Uncommon:
18. Polyuria or polydipsia
19. Hypotension
20. Respiratory arrest or death

Question 144

Differential Diagnoses for Hypocalcemia

x8

Answer 144

Hypoalbuminemia
Chronic renal failure
Eclampsia
Acute kidney injury
Pancreatitis
Soft tissue trauma or rhabdomyolysis
Hypoparathyroidism
Intestinal malabsorption, PLE, starvation

theres like so many

Question 145

HypoCa++ tx

Answer 145

– HyperMg++ and hypOMg++ can impair the secretion of PTH and PTH actions on its receptor, so measurement of serum magnesium (preferably ionized magnesium) is important, especially in animals with refractory hypocalcemia
– treat the primary disease causing the disorder
– typically involves the administration of calcium salts, as well as vitamin D metabolites

Question 146

possible complications of ionized hypocalcemia

Answer 146

severe ionized hypocalcemia can be life threatening because of myocardial failure and respiratory arrest
tachycardia
ECG alterations (i.e., prolonged QT interval)
refractory hypotension
respiratory arrest

Question 147

Serum Mg++

Answer 147

less than 1% of total body magnesium is in the serum, serum magnesium concentrations do not always reflect total body magnesium stores
– normal serum magnesium concentration can occur when there is a total body magnesium deficiency.
– ionized, anion-complexed, and protein-bound fractions.

Question 148

Where does Mg++ reside in the body?

Answer 148

– second most abundant intracellular cation, exceeded only by potassium
Most of the magnesium is found in bone and muscle.
60% of total body magnesium content is present in bone.
20% is in skeletal muscle
remainder is in other tissues, primarily the heart and liver

Question 149

Mg++ Bodily uses

#5

Answer 149

1. required for many metabolic functions
2. production and use of ATP
3. essential for protein and nucleic acid synthesis
4. regulation of vascular smooth muscle tone cellular second messenger systems
5. signal transduction

Question 150

Magnesium homeostasis

Answer 150

achieved through intestinal absorption and renal excretion
– Absorption occurs primarily in the small intestine (jejunum and ileum)

Question 151

Renal managment of Mg++

Answer 151

LOH and DCT are the main sites of magnesium reabsorption in the kidney
– kidney is the main regulator of serum magnesium concentration and total body magnesium content
regulation is achieved by both glomerular filtration and tubular reabsorption

Question 152

Lactation effects on Mg++

Answer 152

Increased concentrations of PTH, in addition to calcium concentration, most likely participate in magnesium conservation during lactation to supply the mammary glands with a sufficient amount

Question 153

Hypomagnesemia Causes

#6

Answer 153

1. Decreased Intake
2. perioperative feline renal transplant recipients cats with diabetes mellitus and diabetic ketoacidosis
3. receiving peritoneal dialysis
4. dogs with congestive heart failure receiving furosemide therapy
5. protein-losing enteropathy
6. lactating dogs

Magnesium losses can occur through the GI tract, kidneys, or both.

Question 154

HypoMg++: Increased Losses

Answer 154

GIT: inflammatory bowel disease, malabsorptive or short-bowel syndromes, or other diseases that cause prolonged diarrhea.

Question 155

HypoMg++: Renal

Answer 155

Acute renal dysfunction as a consequence of glomerulonephritis or the nonoliguric phase of acute tubular necrosis is often associated with a rise in the fractional excretion of magnesium

Question 156

HypoMg++: Drugs

Answer 156

diuretic agents (furosemide, thiazides, mannitol) induce hypomagnesemia by increasing urinary excretion
– aminoglycosides, amphotericin B, cisplatin, and cyclosporine

Question 157

Clinical signs: HypoMg++

Answer 157

changes in resting membrane potential, signal transduction, and smooth muscle tone
– effects of magnesium on the myocardium are linked to its role as a regulator of other electrolytes, primarily calcium and potassium
– cardiac arrhythmias, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, and ventricular fibrillation

Question 158

EKG abnormalities from HypoMg++

Answer 158

– prolongs conduction through the atrioventricular node
– prolongation of the PR interval, widening of the QRS complex, depression of the ST segment, and peaking of the T wave

Question 159

Neuromuscular effects of HypoMg++

Answer 159

increases acetylcholine release from nerve terminals and enhances the excitability of nerve and muscle membranes
– increases the intracellular calcium content in skeletal muscle
– generalized muscle weakness, muscle fasciculations, ataxia, and seizures
– Esophageal or respiratory muscle weakness can be manifested as dysphagia or dyspnea

Question 160

Refractory HypoK+

Answer 160

hypokalemia that is refractory to aggressive potassium supplementation may be due to magnesium deficiency causing excessive potassium loss through the kidneys

Question 161

HypoCa++ from HypoMg++

Answer 161

hypomagnesemia impairs PTH release and enhances calcium movement from extracellular fluid to bone
– total and ionized hypocalcemia often accompanies magnesium depletion
– clinical signs of hypocalcemia seen with hypoMg++ possible

Question 162

HypoMg++ tx

Answer 162

Parenteral administration of magnesium sulfate may result in hypocalcemia because of chelation of calcium with sulfate
= magnesium chloride should be given if hypocalcemia is also present

Question 163

Side effects of Mg++ supplementation

Answer 163

– hypotension, atrioventricular block, and bundle branch blocks
– usually are associated with intravenous boluses rather than CRIs

Question 164

HyperMg++ causes

#3

Answer 164

renal failure/kidney injury, endocrinopathies, and iatrogenic overdose, especially in patients with impaired renal function
– degree of hypermagnesemia parallels the degree of renal failure

Question 165

Clinical signs HyperMg++

Answer 165

– lethargy, depression, and weakness
– Other clinical signs reflect the electrolyte’s action on the nervous and cardiovascular systems
– hyporeflexia = decreased skeletal muscle response
– respiratory depression secondary to respiratory muscle paralysis in w/ profound elevation
– blockade of the autonomic nervous system

Question 166

EKG abnormalities with HyperMg++

Answer 166

– prolongation of the PR interval and widening of the QRS complex due to delayed atrioventricular and interventricular conduction.
– Bradycardia
– severely high serum magnesium concentrations, complete heart block and asystole can occur

Question 167

HyperMg++ tx

Answer 167

– Saline diuresis and furosemide can also be used to accelerate renal magnesium excretion
– severe cases involving unresponsiveness treated with intravenous calcium
– Calcium is a direct antagonist of magnesium at the neuromuscular junction and may be beneficial in reversing the CVS effects of hypermagnesemia
– anticholinesterase treatment may be administered to offset the neurotoxic effects (Physostigmine)

Question 168

Phosphorus Homeostasis

soo manyyy

Answer 168

– body’s major intracellular anion
– essential for the production of ATP, guanosine triphosphate, cyclic adenosine monophosphate, and phosphocreatine, all of which function to maintain cellular membrane integrity, energy stores, metabolic processes, and biochemical messenger systems
– maintenance of normal bone and teeth matrix in the form of hydroxyapatite
– regulation of tissue oxygenation by way of 2,3-di-phosphoglycerate (2,3-DPG)
– support of cellular membrane structure
– buffering acidotic conditions

Question 169

Distribution of Phosphorus in the body

Organic vs Inorganic

Answer 169

• 80% to 85% in the bone and teeth as inorganic hydroxyapatite
• 14% to 15% in soft tissues
• less than 1% in the extracellular space
  – Phosphorus is present in the body as organic and inorganic phosphates
  – Organic phosphate is mostly intracellular and inorganic phosphate is mostly extracellular.

Question 170

Inorganic phosphate

Answer 170

Inorganic phosphate in the form of 2,3-DPG accounts for 70% to 80% of phosphate in RBCs
– Inorganic phosphate is further divided into orthophosphates and pyrophosphates
– most extracellular inorganic phosphate is in the form of orthophosphates

Question 171

Organic Phosphate

Answer 171

components of phospholipids, phosphoproteins, nucleic acids, enzymes, cofactors
– two-thirds of organic phosphate is in the form of phospholipids

Question 172

Which type of phosphate do blood chemical analyzers measure?

Answer 172

blood chemistry analyzers only measure the inorganic phosphates

Question 173

Phosphate regulation

Answer 173

60% to 70% of ingested phosphate is absorbed in small intestine
– Serum phosphate balance is dependent on GFR and tubular reabsorption in PCT
– amount of phosphate reabsorbed is dependent on dietary intake

Question 174

Effects of hormones on Phosphorus

Answer 174

– (PTH) is a phosphaturic hormone because it decreases the tubular transport maximum for phosphate reabsorption
– Growth hormone, insulin, insulin-like growth factor 1, and thyroxine increase tubular phosphate reabsorption
– Growth hormone partially accounts for the expected hyperphosphatemia in young, growing animals

Question 175

Body’s phosphate reservior

Answer 175

skeleton is the body’s phosphate reservoir and provides a readily available source of phosphate during periods of hypophosphatemia under the regulation of PTH and calcitonin

Question 176

HypoPhos- Causes

#4

Answer 176

1. Decreased Gastrointestinal Absorption
2. Transcellular Shifts
3. Increased Urinary Loss
4. Spurious or Laboratory Error

Question 177

Transcellular Shifts of Phos-

#7

Answer 177

associated with:
1. alkalemia,
1. hyperventilation,
1. refeeding syndrome,
1. parenteral nutrition,
1. insulin administration,
1. glucose administration,
1. catecholamine administration or release, and salicylate toxicity

Question 178

Refeeding syndrome effects on Phos-

Answer 178

Hypophosphatemia is the **most common and critical electrolyte disturbance associated with refeeding syndrome. **
During chronic malnutrition, phosphate depletion can occur and may not be reflected by a decrease in serum phosphate concentration.
Administration of enteral or parental nutrition to a patient with chronic malnutrition stimulates insulin release, which promotes intracellular uptake of phosphate and glucose for glycolysis;
– this transcellular shift may result in severe hypophosphatemia.

Question 179

Insulin and Glucose effects on Phos-

Answer 179

– Insulin and glucose administration can cause severe hypophosphatemia in a patient with total body phosphate depletion
– stimulate glycolysis, promoting the synthesis of phosphorylated glucose compounds and intracellular shifts of phosphate.

Question 180

Cellular effects of HypoPhos-

Answer 180

severe hypophosphatemia and total body phosphate depletion can result in widespread cellular dysfunction
– Hemolysis can occur with severe hypophosphatemia because of decreased concentrations of red blood cell ATP and 2,3-DPG, spherocytosis
– Decreased intracellular 2,3-DPG = impairs release of oxygen by hemoglobin to tissues, = tissue hypoxia
– chemotaxis, phagocytosis, and bactericidal activity of leukocytes, which increases the risk of infection in critically ill animals

O2/Hb CURVE

Question 181

CS of HypoPhos-

Answer 181

– skeletal muscle changes include generalized weakness, tremors, and muscle pain
– Rhabdomyolysis (breakdown of muscle tissue) secondary to acute hypophosphatemia from refreeding syndrome
– Neurologic signs may include ataxia, seizures, and coma associated with metabolic encephalopathy

Question 182

HyperPhos- causes

Answer 182

decreased renal excretion
increased intake
iatrogenic administration, and transcellular shifts
– decreased excretion are AKI, acute-on-chronic kidney disease, urethral obstruction, and uroabdomen

Question 183

HyperPhos- from transcellular shifts of phosphate

Answer 183

– occur with tumor lysis syndrome, rhabdomyolysis, and hemolysis
– Tumor lysis syndrome is the clinical manifestation and laboratory sequelae of acute death of tumor cells that release potassium, phosphate, and nucleic acids into circulation and may cause AKI

Question 184

Rhabdomyolysis causing HyperPhos-

Answer 184

syndrome of massive skeletal muscle tissue injury
– can cause hyperphosphatemia directly from release of intracellular contents and indirectly by decreased renal excretion from resulting myoglobin-induced AKI (although is rare in cats or dogs).

Question 185

Iatrogenic overdose of Phosphorus

Answer 185

large doses of parenteral phosphate can cause not only hyperphosphatemia but also hypomagnesemia, hypocalcemia, and hypotension
– Ingestion of cholecalciferol rodenticides and vitamin D3 skin creams (e.g., calcipotriene) can rapidly increase serum phosphate concentration by increased intestinal absorption and release from bones

Question 186

CS of HyperPhos-

Answer 186

anorexia, nausea, vomiting, weakness, tetany, seizures, and dysrhythmias
– Clinical manifestations of hyperphosphatemia predominantly are due to hypocalcemia and ectopic soft tissue calcification

Question 187

Soft tissue effects from HyperPhos-

Answer 187

Soft tissue calcium phosphate accumulation occurs when the calcium phosphate product is greater than 58 to 70 mg2/dl2
– Tissues primarily affected by ectopic calcification include cardiac, vasculature, renal tubules, pulmonary, articular, periarticular, conjunctival, skeletal muscle, and skin

Question 188

EKG abnormalities from HyperPhos-

Answer 188

Arrhythmias:
polymorphic ventricular tachycardia or torsades de pointes caused by prolongation of the QT interval, are also associated with subsequent hypocalcemia and hypomagnesemia

Question 189

pH relationship with HCO3- and CO2

Answer 189

pH has a direct relationship with bicarbonate concentration and an inverse relationship with PCO2

Question 190

three major processes for acid-base balance:

Answer 190

1. regulation of PCO2 by alveolar ventilation (respiratory component)
2. buffering of acids by bicarbonate nonbicarbonate buffer systems (metabolic component)
3. changes in renal excretion of acid or base

Question 191

Henderson-Hasselbalch equation

Answer 191

uses pH, PCO2 and bicarbonate concentration for carbonic acid (H2CO3)
– pH is the consequence of the ratio of bicarbonate to PCO2.

Question 192

PCO2

Answer 192

Carbon dioxide acts as an acid in the body because of its ability to react with water to produce carbonic acid (H2CO3)
– increases in PCO2, the ratio of bicarbonate to PCO2 is decreased; hence pH falls.

Question 193

carbonic acid equation

Answer 193

CO2 + H2o ←→ H2CO3 ←→ H+ + HCO3-

• increases in PCO2, the ratio of bicarbonate to PCO2 is decreased; hence pH falls.
• with an increase in PCO2, the carbonic acid equation (below) will be driven to the right, increasing the hydrogen ion concentration

Question 194

Bicarbonate

Answer 194

– Elevations in bicarbonate concentration will drive the pH higher and represent a metabolic alkalosis while decreases in bicarbonate concentration represent a metabolic acidosis
– elevations in PCO2 will lead to elevations in bicarbonate while decreases in PCO2 will lead to a decrease in bicarbonate

Question 195

Base excess

Increased vs Decreased amount

Definition

Answer 195

defined as the amount of strong acid or strong base (in mmol/L) that must be added to 1 liter of fully oxygenated whole blood **to restore the pH to 7.4 **
– increased BE (more positive value) is consistent with a metabolic alkalosis (either gain of bicarbonate or loss of acid)
– decreased BE (more negative value) represents a metabolic acidosis

Question 196

Base Excess relationship with PCO2

Answer 196

– advantage of using BE over bicarbonate concentration is that it is independent of changes in the respiratory system
– minimal changes in PCO2 present, the BE and bicarbonate should correlate well
– with substantial abnormalities in PCO2, the BE is a more reliable measure of the metabolic component

Question 197

Total carbon dioxide

what does it represent?

Answer 197

– represents the metabolic acid-base component, not the respiratory system component
– measure of all the CO2 in a blood sample, and the majority of CO2 is carried as bicarbonate in the blood

Question 198

Anion gap definition

Answer 198

– Electroneutrality requires there to be an equal number of anions and cations in a physiologic system
– In reality there is no actual AG; the apparent AG exists because more cations in the system are readily measured than anions
– reflection of unmeasured ions

Question 199

Metabolic Acidosis: 1st mechanism

Answer 199

– Bicarbonate concentration can fall with a rise in chloride concentration = hyperchloremic metabolic acidosis
– due to disease processes causing bicarbonate loss in the gastrointestinal tract, or kidneys or can be iatrogenic, secondary to administration of sodium chloride

Question 200

Metabolic Acidosis: 2nd mechanism

Answer 200

occur from the gain of acid
→ excess acid in the system, hydrogen ions will titrate (combine) with bicarbonate, leading to a fall in bicarbonate concentration
– anion that accompanies the hydrogen ion (the conjugate base) will accumulate, maintaining electroneutrality and increasing the AG

Question 201

HAGMA

Answer 201

High Anion Gap Metabolic Acidosis
– common causes of increased AG metabolic acidosis in small animals is DUEL
– AG can be calculated in an effort to help determine the underlying cause of the abnormality, assuming the patient is not hypoalbuminemic

Question 202

DUEL causes for HAGMA

Answer 202

Diabetic ketoacidosis
Uremic acids
Ethylene glycol toxicity
Lactic acidosis

Question 203

Hyperchloremic Metabolic Acidosis causes

Answer 203

• Renal bicarbonate loss
• Gastrointestinal bicarbonate loss
• Sodium chloride administration
• Hypoadrenocorticism

Question 204

Normal unmeasured anions

Answer 204

Albumin and phosphorus
– states of hypoalbuminemia, abnormal unmeasured anions (e.g., lactate or ketones) may be present, but the calculated AG may remain within the reported normal range
– AG is not reliable in hypoalbuminemic patients
– Conversely, hyperalbuminemia will increase AG

Question 205

Mixed Acid-Base disorder

Answer 205

– abnormality in both the metabolic and respiratory components
– evident when both the respiratory and metabolic components have the same influence on acid-base balance (i.e., metabolic acidosis and respiratory acidosis or metabolic alkalosis and respiratory alkalosis)
– also present when there are abnormalities evident in both the metabolic and respiratory components, but the pH is in the normal range

Question 206

Respiratory acidosis

Answer 206

– results from an imbalance in CO2 production via metabolism and CO2 excretion via alveolar minute ventilation of the lung
– consequence of increased CO2 production or decreased alveolar ventilation
– diseases that reduce respiratory rate, tidal volume, or both
– Diseases that prevent the transmission of impulses from the respiratory center to the respiratory muscles, such as cervical spinal cord disease, peripheral neuropathies and diseases of the neuromuscular junction, can all cause respiratory paralysis and respiratory acidosis
– severe cases require MV

Question 207

Respiratory alkalosis

Dz process that cause Resp Alk

Answer 207

– decreased PCO2 is the result of an increase in VA
– disease processes that may stimulate an increased respiratory rate and/or tidal volume
– include significant hypoxemia, pulmonary parenchymal disease (causing stimulation of stretch receptors or nociceptors), and airway inflammation
– central stimulation of respiratory rate and effort by the respiratory center → pathologic process resulting from brain injury, or it could be behavioral as a result of pain or anxiety.

Question 208

What accurately determines Ventilatory status?

Answer 208

most accurately determined by measurement of PaCO2.
– PvCO2 can be used to evaluate ventilation if the animal is cardiovascularly stable

Question 209

Metabolic acidosis

Question 210

renal tubular acidosis (RTA)

causes

Distal vs Proximal

Answer 210

Renal loss of bicarbonate from proximal or distal tubular dysfunction
– proximal RTA, there is inadequate reabsorption of bicarbonate in the proximal nephron
– Distal RTA is a disorder involving inadequate hydrogen ion secretion in the distal tubule that prevents maximal acidification of the urine

pyelonephritis and IMHA

Fanconi syndrome - congenital dz

Renal loss of bicarbonate can be an appropriate response to a persistent respiratory alkalosis (metabolic compensation)

Question 211

Metabolic acidosis tx

Answer 211

– Fluids containing a buffer such as lactated Ringer’s solution will aid in the metabolism of hydrogen ions
– hyperchloremic metabolic acidosis, use of lower chloride containing fluids (i.e., avoiding 0.9% NaCl) will also be of benefit.
– Treatment of metabolic acidosis due to an acid gain is primarily focused on the resolution of the underlying cause and appropriate selection of IV fluid therapy (DKA)

Question 212

When would bicarb administration be warranted?

Answer 212

When the acidosis is severe or the compensatory respiratory alkalosis is considered detrimental to the patient, bicarbonate administration is indicated

Question 213

Metabolic alkalosis

Answer 213

Metabolic alkalosis can broadly be considered to occur due to either acid loss or bicarbonate gain
– Causes of acid loss include selective gastric acid loss such as can occur with gastrointestinal obstructive processes, excessive nasogastric tube suctioning
– Renal acid loss can occur due to loop diuretic administration, mineralocorticoid excess, and the presence of nonresorbable anions such as carbenicillins

Question 214

Cl- relationship with Metabolic Alkalosis

Answer 214

Acid loss invariably occurs along with chloride in the gastrointestinal tract and renal system, and as a result, many animals with metabolic alkalosis will also be hypochloremic

Question 215

K+ relationship with Metabolic Alkalosis

Answer 215

Hypokalemia can play a significant role in the generation and maintenance of metabolic alkalosis.
– Intracellular shifts of hydrogen ions in exchange for potassium ions leaving the cells will increase the pH of the extracellular fluid.
– hypokalemia promotes renal acid loss
– converse is true with acidemia

Question 216

K+/H+ exchange

Answer 216

– cells exchange hydrogen ion for a potassium ion, using a special ion transporter located across the cell membrane.
– in order to help compensate for an acidosis, hydrogen ions enter cells and potassium ions leave the cells and enter the blood
–In the acidotic patient there is a pseudo-hyperkalaemic state that may not reflect the total body potassium
– Converse is true for alkalosis

Question 217

Renal production of Bicarb

Answer 217

kidney has the ability to excrete large quantities of bicarbonate, such that metabolic alkalosis should be rectified rapidly.
When metabolic alkalosis is persistent, there must be factors limiting renal bicarbonate excretion

Question 218

What process can affect Renal bicarb production?

#4

Answer 218

Decreased effective circulating volume
hypochloremia can both limit renal bicarbonate excretion.
Hypokalemia and aldosterone excess further impair renal bicarbonate excretion

Question 219

Consequences of Metabolic Acidosis

#7

Answer 219

1. decreased myocardial contractility
2. arterial vasodilation
3. impaired coagulation
4. increased work of breathing secondary to carbon dioxide production
5. decreased renal and hepatic blood flow
6. insulin resistance
7. altered central nervous function

Question 220

Bicarbonate therapy

when is it contraindicated?

Answer 220

bicarbonate binds hydrogen ions (hence the alkalinizing effect) to form carbonic acid → this rapidly dissociates to CO2 and water
– If ventilation does not increase appropriately, an elevated PCO2 will cause a decrease in pH
– contraindicated in patients with evidence of hypoventilation

Question 221

Adverse effects of Bicarb therapy

#11

Answer 221

1. Increased hemoglobin affinity for oxygen
2. Increased blood lactate concentration
3. Paradoxical intracellular acidosis
4. Hypercapnia
5. Hypervolemia
6. Hyperosmolality
7. Hypernatremia
8. Hypocalcemia (ionized)
9. Hypomagnesemia (ionized)
10. Hypokalemia
11. Phlebitis

Question 222

paradoxical intracellular acidosis

Answer 222

Bicarbonate cannot freely cross cell membranes, but the CO2 produced as bicarbonate is metabolized can freely enter cells
– Once intracellular, the CO2 combines with water leading to hydrogen ion release, causing intracellular acidosis
– evidence shows decreases in cellular and cerebrospinal fluid pH following bicarbonate therapy

Question 223

strong ion difference approach

#3 components

Answer 223

1. partial pressure of carbon dioxide (PCO2)
2. the difference between strong cations and strong anions, known as the SID
3. total nonvolatile weak acids

(sodium + potassium) − (chloride)

Question 224

Strong ion difference

Definition
Ions included

Answer 224

ions that are fully dissociated at physiologic pH
– major strong ions include sodium, potassium, calcium, magnesium, and chloride
– sodium and chloride are the most important strong ions in the body and SID is commonly simplified as the difference between serum sodium and chloride concentrations

Question 225

Decreased SID metabolic acidosis

Causes
fluid tx choice

Answer 225

due to hyponatremia, hyperchloremia, or a combination of the two
– may be best treated with an IV fluid with a higher SID, such as lactated Ringer’s with an effective SID of approximately 28mmol/L (after the lactate is metabolized)

Question 226

increased SID metabolic alkalosis

Causes
fluid tx choice

Answer 226

due to hypernatremia, hypochloremia, or both
– may benefit from a fluid with a low SID such as 0.9% saline (SID = 0)

Question 227

Total weak acids (ATOT)

Definition
Ions involved

Answer 227

Weak acids are only partially dissociated at physiologic pH.
The major contributors to ATOT are albumin and phosphorus
– increases in ATOT = metabolic acidosis
– decreases in ATOT (primarily from decreased albumin) = metabolic alkalosis

Question 228

Strong ion gap

Answer 228

evaluation of unmeasured anions in the SID approach and is similar to the use of anion gap (AG)
– if there are no unmeasured anions (SIG = 0) in the system
– unmeasured anions will cause a more positive value for SIG
SIGsimplified = [albumin] × 4.9 – AG
SIGsimplified = [albumin] × 7.4 − AG

Question 229

Free water effect

Excess vs deficit

Answer 229

free water effect on BE is due to changes in the water balance
– free water concentration is reflected by sodium concentration
– deficit of free water causing hypernatremia = positive FWE indicating an alkalinizing effect—a contraction alkalosis.
– excess of free water causing hyponatremia = negative FWE indicating an acidotic effect—a dilutional acidosis.

Question 230

Chloride effect

Answer 230

chloride and bicarbonate are reciprocally linked (i.e., when a chloride ion is excreted, a bicarbonate ion is retained and vice versa)
– gastric acid secretion, intestinal bicarbonate secretion, renal acid-base handling, and transcellular ion exchange
– Positive or negative effect

Question 231

Positive Chloride effect

Answer 231

increased (positive) chloride effect (reflecting hypochloremia) is associated with a process that increases bicarbonate concentration and is indicative of an alkalinizing process

Question 232

Negative Chloride effect

Answer 232

decreased chloride effect (negative) marks an acidotic process

Question 233

Albumin effect

Answer 233

Albumin acts as a weak acid and
has many H+ binding sites
– Alkalizing effect = Hypoalbuminemia is equivalent to the removal of a weak acid from the system; it will be evident as a positive effect
– Acidifying effect = hyperalbuminemia will be evident as a negative effect, indicating an acidotic influence.

Question 234

Phosphorus effect

Answer 234

Phosphoric and sulfuric acids are products of protein metabolism and are normally excreted by the kidneys.
– AKI or failure retain these acids, resulting in a metabolic acidosis
– Elevated phosphorus will cause a negative effect and indicates an acidotic influence on BE
– hypophosphatemia does not cause a clinically significant alkalosis

Question 235

Lactate effect

Answer 235

– produced from the conversion of pyruvate by lactate dehydrogenase, a reaction that consumes hydrogen ions
– Acidosis = accumulation of hydrogen ions from the hydrolysis of ATP
– In diseases where mitochondrial function is impaired, such as cellular hypoxia, there is accumulation of both lactate and hydrogen ions leading to lactic acidosis
– elevation = negative effect = acidic influence on BE

Question 236

Lactate definition

Answer 236

• Lactate is an intermediary metabolite of glucose oxidation that serves as a carbohydrate energy substrate reservoir.
• it is produced in the cytosol and then either converted back to pyruvate to proceed through local aerobic cellular metabolism or exported out of the cell and transported to distant tissues in the bloodstream
• all tissues are capable of producing lactate

Question 237

Glycolysis

With Normal O2 present

Answer 237

Glycolysis is the cytosolic process (which occurs in the presence or absence of oxygen) by which 1 mole of glucose is oxidized to 2 moles of pyruvate, ATP, and reduced nicotinamide adenine dinucleotide (NADH)
– Glycolysis consumes NAD+ and produces NADH and pyruvate

Question 238

Pyruvate

With normal O2 present

Answer 238

With Glycolysis:
normal aerobic conditions = only a small quantity of pyruvate is converted into lactate, catalyzed by lactate dehydrogenase (LDH)
– Ultimately lactate is either converted back into pyruvate in local or distant tissues and oxidized to produce energy or converted back into glucose by gluconeogenesis

Question 239

How many moles of ATP is normally produced?

with normal O2 present

Answer 239

WITH NORMAL O2 PRESENT = Pyruvate enters the mitochondria and is converted into acetyl CoA, the tricarboxylic acid (TCA) cycle, the electron transport chain, and oxidative phosphorylation to produce 36 moles of ATP

Question 240

TCA cycle with inadequate O2 available

How many ATP mole produced?

Answer 240

To allow glycolysis to continue, NAD+ is replenished and pyruvate and H+ ions are removed by conversion of pyruvate to lactate
– only 2 moles of ATP per glucose molecule,

Question 241

How does lactatic acidosis form?

Answer 241

When the ATP made by glycolysis is utilized, H+ is released into the cytosol
– if oxygen supplies are insufficient, this cannot happen and H+ ions accumulate and are then transported out of the cell.
– acidosis from increased lactate production is mostly due to reduced H+ consumption, not increased lactate production per se.

Question 242

Lactate and Be Relationship

Answer 242

each 1mmol/L increase in lactate is associated with a concomitant reduction of the standardized base excess of 1mmol/L.

Question 243

Lacate metabolism

Answer 243

Under conditions of health and aerobiosis, the liver and renal cortex are the predominant lactate-consuming organs
– Hepatic metabolism accounts for 30% to 60% of lactate consumption, and the liver is capable of metabolizing markedly increased lactate loads
– It is reabsorbed by the proximal convoluted tubule, and the renal threshold is 6 to 10mmol/L.12-14

Question 244

Whole blood lactate measurement

Answer 244

Whole blood lactate refers to the mean of intraerythrocytic and plasma lactate

Question 245

Type A HyperLactatemia

Answer 245

Increased Oxygen Demand:
* Exercise
* Trembling/shivering
* Muscle tremors
* Seizure activity
* Struggling
Decreased Oxygen Delivery:
* Systemic hypoperfusion
* Local hypoperfusion
* Severe anemia
* Severe hypoxemia
* Carbon monoxide poisoning

Question 246

Type B1 HyperLactatemia

Answer 246

B1: Associated with Underlying Disease
* Sepsis
* Neoplasia
* Diabetes mellitus
* Liver disease
* Thiamine deficiency
* Pheochromocytoma
* Hyperthyroidism
* Alkalosis

Question 247

Type B2 HyperLactatemia

List as many as you can

Answer 247

B2: Associated with Drugs or Toxins
* Acetaminophen
* Activated charcoal
* β2 agonists
* Bicarbonate
* Corticosteroids
* Cyanide
* Epinephrine
* Ethanol
* Ethylene gylcol
* Glucose
* Insulin
* Lactulose
* Methanol
* Methylxanthines
* Nitroprusside
* Propofol
* Propylene glycol
* Salicylates
* Strychnine
* Sorbitol
* TPN
* Xylitol

Question 248

Type B3 HyperLactatemia

Answer 248

B3: Inborn Errors in Metabolism
* Mitochondrial myopathies
* Enzymatic deficiencies
* MELAS

Question 249

When does HyperLactatemia develop with anemia?

Answer 249

– Anemia-related hyperlactatemia is highly dependent on intravascular volume status and chronicity
– acute, severe, euvolemic anemia, hyperlactatemia does not develop until the packed cell volume (PCV) drops below 15%.

Question 250

When is HyperLactatemia seen with hypoxemia?

Answer 250

hypoxemia must also be very severe (partial pressure of oxygen [PaO2] 25 to 40mm Hg) before pure hypoxemia-related hyperlactatemia develops

Question 251

Relationship between hyperlactatemia with hypoperfusion

Answer 251

progressively worsening hypoperfusion shows a fairly linear relationship with plasma lactate concentration

Question 252

Sepsis HyperLactatemia mechanisms

Answer 252

Suggested mechanisms include stimulation of: skeletal muscle Na+/K+-ATPase by catecholamines
mitochondrial dysfunction → direct cytochrome inhibition
increased hepatic lactate production;
reduced hepatic lactate extraction;
impaired tissue oxygen extraction
and capillary shunting

Question 253

Relationship between glycolysis and hyperlactatemia?

Answer 253

increased aerobic glycolysis secondary to adrenergic stimulation significantly contributes to sepsis-associated hyperlactatemia

Question 254

Neoplasia associated Hyperlactatemia

Answer 254

Hyperlactatemia associated with neoplasia may be due to hypoperfusion in some cases, but malignant cells are known to exhibit atypical carbohydrate metabolism by preferentially utilizing glycolytic pathways for energy production despite sufficient oxygen availability (Warburg effect)

Question 255

How does Epinephrine cause HyperLactatemia

Answer 255

Epinephrine increases Na+/K+-ATPase activity and glycogenolysis resulting in hyperlactatemia
– conditions resulting in excess endogenous catecholamine release, such as pheochromocytoma, have also been associated with hyperlactatemia

Question 256

Dog Breeds reporte to develop Type 3 Hyperlactatemia

Answer 256

Mitochondrial myopathies have been reported in the Jack Russell Terrier, German Shepherd, and Old English Sheepdog
– Pyruvate dehydrogenase deficiency has been recognized in the Clumber Spaniel and Sussex Spaniel

Question 257

Cryptic shock

Answer 257

term cryptic shock has been used to describe ill or injured patients with high lactate concentrations without hypotension

Question 258

D-lactate

Answer 258

D-Lactate is not detected by routine lactate analyzers and can only be measured by specialist laboratories
– Both D- and L-lactate are produced by some bacteria under anaerobic conditions
– In people, D-hyperlactatemia associated with short bowel syndrome and exocrine pancreatic disease is thought to contribute to encephalopathy

Question 259

Correlation between muscle activity and lactate

Answer 259

higher levels of muscle activity can significantly increase lactate (e.g., lots of struggling, trembling, tremors, marked exercise, and seizures).

Question 260

Urine Osmolality

Answer 260

Measurement of urine osmolality and electrolyte concentration can provide valuable insight regarding water balance, effective circulating volume (ECV), and electrolyte and acid-base disorders
– may provide insight into renal handling of water and electrolytes for patients with disturbances in extracellular fluid volume or content
– may be helpful in determining the nature of a patient’s polyuria and evaluating specific serum electrolyte abnormalities
– determining cause for hypoNa+

Question 261

Urine Na+

Answer 261

Assessment of ECV
< 20, Decreased ECV (Na avid)
Aldosterone presence

Question 262

Urine Cl-

Answer 262

Assessment of ECV
Assessment of metabolic alkalosis
< 15–25 = Chloride responsive metabolic alkalosis
>15–25 = Chloride unresponsive metabolic alkalosis

Question 263

Urine K+

Answer 263

Assessment of Hypokalemia
< 15–20 = Nonrenal K loss
>40 = Renal K wasting
Hyperkalemia
>40 = Nonrenal cause (e.g., hypoadrenocorticism)

Question 264

Free water clearance
Urine Osmolality

Answer 264

Assessment of solute free water excretion
Positive = Free water excretion (absence of ADH secretion and/or response)
Negative = Free water retention (ADH secretion and response)

Question 265

total body water

Answer 265

– continuously in flux because it is being lost through evaporation, elimination, and metabolic processes and gained from food and water intake
– volume and distribution of TBW are under the control of hormonal mechanisms that maintain water and sodium balance by regulating renal water and salt excretion and reabsorption, whereas thirst mechanisms influence water intake

Question 266

Hormone detection of Fluid loss

Answer 266

Loss of fluid with little or no solute (i.e., hypotonic fluid loss) will increase plasma solutes per kilogram water (osmolality).
– increase in the plasma osmolality is detected by the supraoptic and paraventricular nuclei in the hypothalamus = release of antidiuretic hormone (ADH; arginine vasopressin),

Question 267

Renal conservation of water and sodium is stimulated by:

Answer 267

Hypovolemia stimulates baroreceptors that cause the hypothalamic-pituitary-adrenal axis to produce and release ADH, aldosterone, renin, and cortisol = renal water/Na+ conservation

Question 268

Renal water and sodium excretion is stimulated by:

Answer 268

overexpansion of the cardiovascular system causes stretch of the atria and release of atrial natriuretic peptide = increase in renal water/Na+ excretion

Question 269

Correlation between TBW and body mass

Answer 269

Ninety percent of acute changes in body mass can be attributed to a change in TBW
– 1kg change in TBW may be equivalent to 1L change in TBW

Question 270

Interstitial volume changes

Answer 270

examining mucous membrane moisture, skin tent response, eye position, and corneal moisture
– minimum degree of interstitial dehydration that can be detected in the average patient is approximately 5% of body weight
– greater than 12% is likely to be fatal

Question 271

5%–6% Interstitial Dehydration exam findings

Answer 271

Tacky mucous membranes ± some change in skin turgor

Question 272

6%–8% Interstitial Dehydration exam findings

Answer 272

Mild decreased skin turgor
Dry mucous membranes

Question 273

8%–10% Interstitial Dehydration exam findings

Answer 273

Obvious decreased skin turgor
Retracted globes within orbits

Question 274

10%–12% Interstitial Dehydration exam findings

Answer 274

Persistent skin tent due to complete loss of skin elasticity
Dull corneas
Evidence of hypovolemia

Question 275

Interstitial overhydration

Answer 275

increased turgor of the skin and subcutaneous tissue, giving it a gelatinous character; peripheral or ventral pitting edema can also occur.
Chemosis and clear nasal discharge may also be evident

Question 276

Intravascular volume changes

Answer 276

– assessed through the examination of perfusion parameters (MM color, capillary refill time, heart rate, and pulse quality) and determination of jugular venous distensibility
– rapid intravascular losses such as hemorrhage can cause hypovolemia without causing clinically detectable changes in the interstitial fluid compartment

Question 277

Intracellular volume changes

Answer 277

cannot be identified on physical examination
– rely on changes in the effective osmolality of ECF (primarily changes in sodium concentration) to mark changes in cell volume
– With decreases in ECF effective osmolality = movement of water into the ICF compartment = increase in intracellular volume
– increases in ECF effective osmolality = decreases in intracellular volume

Question 278

Hypotonic fluid loss

How does this occur? what will it cause? what systems does it affect the most?

Answer 278

TBW loss is due to loss of a fluid with little or no salt content (i.e., hypotonic fluid loss) = increases in ECF osmolality, reflected by increases in serum sodium concentration
– water will move from the ICF compartment to the ECF compartment
– loss of ICF volume has the greatest impact on the central nervous system, and if the degree of solute-free water loss is severe and acute it can result in neurologic abnormalities and possibly death as a result of neuronal cell shrinkage

Ex: uncontrolled diabetes insipidus

Question 279

Isotonic fluid loss/gain

Answer 279

net loss or gain of fluid with a salt concentration similar to that of the ECF = changes in the ECF volume with little change in ECF osmolality = no change in the ICF volume
– will lead to interstitial dehydration/overhydration
– minimal change in serum sodium concentration with isotonic fluid gain or loss

Question 280

Urine osmolality and urine specific gravity (USG) measurements for ECF hydration status

Answer 280

Urine osmolality and USG will increase as water is reabsorbed from the urine filtrate in states of ECF dehydration
– decrease as water is excreted from the urine in states of ECF over hydration.
– will be limited if the patient has received IV fluid therapy or diuretic administration before urinalysis

Question 281

Fluid objective administration phases:

#4

Answer 281

resuscitation, optimization, stabilization, and evacuation

Question 282

assessment of static dynamic markers for fluid therapy

Answer 282

For example, the caudal vena cava (CVC) diameter and left atrial to aortic root ratio (LA:Ao) are static markers, while the CVC collapsibility index is a dynamic marker (see below)

Question 283

Fluid Challenges
Passive Leg Raises

Answer 283

– mini-boluses of isotonic crystalloids as low as 3–5 ml/kg, administered within 5 minutes
– PLR shifts the volume from the venous system of the legs to the central circulation, mimicking the effect of a fluid bolus.
– may elicit an adrenergic/sympathetic or white coat response in awake companion animals

Question 284

Venous =

Answer 284

right atrial pressure (RAP), and the resistance to venous flow (Rv) are the main driving forces of venous return and can be expressed through the following formula:

venous return = (MSFP – RAP/Rv)

–other words, venous return can be increased by one of three mechanisms: (1) lowering RAP, (2) decreasing Rv, and (3) increasing MSFP

Question 285

Radiographic assessment of volume status

Answer 285

accuracy of chest radiographs to detect signs of hypo- or hypervolemia through changes in cardiac size, CVC, and pulmonary vessel diameter has been reported at 44% in humans

Question 286

Perfusion parameters

Answer 286

assessed indirectly through upstream and downstream measures of perfusion
(e.g., arterial blood pressure and lactate, respectively)

Question 287

Intravenous volume assement: Cardiac POCUS

Answer 287

dogs with clinical signs of hypovolemia have smaller left ventricular and left atrial lumen sizes, and thicker left ventricular walls
– proportional to the severity of hypovolemia
– increased ventricular wall size, and decreased ventricular and atrial lumen size has been observed in cats following volume depletion (7%–10% body weight), while volume administration results in increasing left atrial and ventricular lumen size

Question 288

fluid responsive patient

Answer 288

(A) will increase preload following a fluid bolus, without a significant increase in extravascular lung water (EVLW). As preload increases, stroke volume (SV) will also increase until the optimal preload is achieved. A fluid nonresponsive patient
(B) will have a marginal to no increase in preload, and thus no improvement in SV, but a significant increase in EVLW

Question 289

Answer 289

Superimposition of the Frank–Starling and Marik–Phillips curves demonstrating the effects of increasing preload on stroke volume (SV) and lung water in a patient who is preload responsive (a)
nonresponsive (b).
With sepsis, the extravascular lung water (EVLW) curve is shifted to the left. CO; cardiac output, CVP; central venous pressure

Question 290

Modified Starling’s forces

Answer 290

hydrostatic and colloid osmotic pressure [COP] in the intraluminal and extraluminal spaces)
– govern the magnitude of fluid filtration from the capillary into the interstitial compartment.

Question 291

What % of Albumin accounts for Plasma COP?

Answer 291

plasma albumin accounts for 80% of plasma COP

Question 292

Crystalloids

Answer 292

fluids containing small solutes with molecular weights less than 500 g/mole
–readily crosses capillary endothelium and equilibrate throughout the ECF compartment.
– lag time of 20 to 30 minutes for electrolytes to distribute evenly in the extracellular fluid compartments

Question 293

Why is 5% Dextrose in water considered “free water?”

Answer 293

5% dextrose in water is considered free water because after dextrose metabolism it does not contain an effective osmole.

Question 294

How much and how long does a crystalloid volume remain in IVS?

Answer 294

Less than one-third of the volume of crystalloids administered remains in the intravascular space 30 minutes after administration.

Question 295

Tonicity effect on osmotic gradient

Answer 295

lower the fluid tonicity, the greater the dilutional effect on extracellular fluid tonicity, resulting in an osmotic gradient favoring free water movement into the intracellular space and leaving less of the administered fluid volume in the extracellular space.

Question 296

Osmolarity of Isotonic fluids

Answer 296

range of 270 to 310 mOsm/L
– do not cause significant fluid shifts between intracellular and extracellular fluid compartments in normal animals

Question 297

Osmolarity of Hypotonic fluids

Answer 297

0.45% saline has an osmolarity of 154 mOsm/L with a sodium [and chloride] concentration of 77 mEq/L each
5% dextrose in free water is a unique isoosmotic solution (252 mOsm/L) with hypotonic effects since dextrose is rapidly metabolized and free water remains (osmolarity of 0 mOsm/L).

Sterile water with an osmolarity of 0 mOsm/L

Question 298

Injectable sterile water adverse effects

Answer 298

should never be administered directly intravenously because of the risk of intravascular hemolysis and endothelial damage

Question 299

Uses for Hypotonic fluids

Answer 299

Hypotonic fluids replenish free water deficits and are useful for treating animals with hypernatremia secondary to hypotonic fluid loss
– distribute throughout both intracellular and extracellular fluid compartments, with less remaining extracellularly in comparison to isotonic fluids

Question 300

Why should you never bolus Hypotonic solutions?

Answer 300

– rapid IV administration of hypotonic fluids drops plasma and ECF osmolarity (mainly determined by sodium level) quickly; consequently, water shifts from the ECF space to the intracellular space
– may also lead to life-threatening cerebral edema

Question 301

Osmolarity of Hpertonic fluids

Answer 301

7.2% HTS = 2566 mOsm/L

Question 302

Hypertonic solution effects on Free water

Answer 302

– causes a free water shift (i.e., osmosis) from the intracellular space to the extracellular space, expanding the extracellular fluid volume by 3 to 5 times the volume administered
– Osmotic fluid shifts from the interstitial space into the intravascular space start immediately after intravenous administration of hypertonic solution
– Free water from the intracellular fluid compartment then moves into the extracellular fluid compartment as the interstitial fluid osmolarity rises

Question 303

Uses for Hypertonic fluids

Answer 303

hypovolemic shock, intracranial hypertension, and severe hyponatremia
– It transiently improves CO and tissue perfusion via arteriolar vasodilation (decreased afterload), volume loading (increased preload), and reduced endothelial swelling, and has a weak positive inotropic effect
– improves cerebral perfusion pressure in head trauma patients by augmenting mean arterial blood pressure and decreasing ICP

Question 304

How long is the intravascular volume expansion effect of HTS?

Answer 304

intravascular volume expansion effect of hypertonic saline is transient (< 30 minutes) because of the redistribution of electrolytes throughout the extravascular space and osmotic diuresis

Question 305

Adverse effects of HTS

Answer 305

rates cannot exceed 1 ml/kg/min because hypotension may result from central vasomotor center inhibition or peripheral vasomotor effects mediated by the acute hyperosmolarity (bradycardia and vasodilation).

Question 306

Acid-base effects of crystalloids

Answer 306

acid-base effects of crystalloid administration depend largely on the buffer content of the fluid
– Acetate and lactate are weak buffers included in some crystalloids such as Normosol-R, LRS, and Plasma-Lyte
– Metabolism of these buffers consumes hydrogen ions, resulting in an alkalinizing effect
– beneficial when treating patients with a metabolic acidosis

Question 307

Colloid definition

Answer 307

Colloid solutions contain large hydrophilic molecules (>10,000 Da) that do not readily cross the vascular endothelium and remain within the intravascular space in patients with an uncompromised, intact vascular barrier

Question 308

revised Starling’s equation

Answer 308

Includes endothelial glycocalyx layer, the endothelial basement membrane, and the extracellular matrix to the tradition principle
– subglycocalyx COP replaces the interstitial fluid COP as a determinant of transendothelial flow

Question 309

traditional Starling’s principle

Answer 309

describes how an increased intravascular to interstitial hydrostatic pressure gradient leads to transvascular fluid flux into the interstitial space at the arteriolar end of the capillary; fluid is subsequently reabsorbed into the intravascular space at venous end of the capillary due to an increased intravascular COP

subglycocalyx COP replaces the interstitial fluid COP as a determinant of transendothelial flow in revised equation

Question 310

Endogenous colloid particles

Answer 310

albumin, globulins, and fibrinogen

Question 311

Synthetic starch colloids

Answer 311

major use of HES solutions is to rapidly expand the intravascular volume with small volume resuscitation by increasing the COP
– HES is synthesized from amylopectin, which is a naturally occurring starch, derived from either potatoes or corn, and is hydroxylated to prevent rapid degradation by α-amylase

Question 312

Natural colloids

Answer 312

fresh frozen plasma (FFP), frozen plasma, cryopoor plasma (CPP), cryoprecipitate (CRYO), human serum albumin (HSA), canine albumin, and intravenous immunoglobulin

Question 313

DKA

When should Phos supplmentation be avoided?

Answer 313

should not be used in conjunction with calcium supplementation.
Overzealous phosphate administration can result in iatrogenic hypocalcemia and associated neuromuscular signs, hypernatremia, hypotension, and diffuse tissue calcification

Question 314

Adverse effects of HCO3- supplementation?

#6

Answer 314

1. paradoxical cerebral acidosis,
2. increased carbon dioxide production and the potential for hypercapnia,
3. increased sodium and osmole concentration, risk for circulatory system overload,
4. iatrogenic metabolic alkalosis,
5. changes to the oxygen dissociation curve (Bohr effect),
6. hypokalemia

Question 315

Why is dextrose used with Insulin administration for DKA?

Answer 315

vital to achieve metabolic breakdown of the remaining ketone bodies and resolve acidosis

Question 316

Neuroglycopenia

Answer 316

a shortage of glucose in the brain thereby affecting the function of neurons and altering brain function and behavior.
Other subtler signs may include pupil dilation, anxiety, or drooling

Question 317

Hyperosmolar Hyperglycemic State

hyperosmolar hyperglycemic non‐ketotic syndrome

Answer 317

characterized by hyperglycemia (blood glucose >600 mg/dL), hyperosmolarity (>350 mOsm/L), and dehydration without the presence of ketoacidosis

normal osmolarity in dogs is approximately 290–310 mOsm/L and 290–330 mOsm/L in the cat.

Question 318

Rehydration protocol for Hyperosmolar/Hyperglycemia syndrome

Answer 318

Sodium concentration should be reduced at a rate no greater than 0.5 mEq/L/h to avoid cerebral edema and worsening of neurological status